Acetonitrile → 3-(2-Bromophenyl)-3-oxopropanenitrile
Reaction equation
[H-].[Na+].[CH3:3][C:4]#[N:5].C[O:7][C:8](=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[Br:15]>C1COCC1>[Br:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:8](=[O:7])[CH2:3][C:4]#[N:5]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a suspension of NaH (60% dispersion, 1.14 g, 28.4 mmol) in dry THF (50 mL) under N2 was added CH3CN followed by 2-bromo-benzoic acid methyl ester (2 mL, 14.2 mmol). The reaction mixture was refluxed for 1.5 hour, then cooled to 0° C., quenched with water (1 mL), and concentrated in vacuo. The residue was diluted with water and the aqueous layer was extracted with hexane (2×), then acidified to pH 3-4 with 1N aqueous HCl. The milky aqueous layer was extracted with CHCl3 (3×), the combined organic layers were dried over sodium sulfate, filtered, and concentrated. Purification on silica gel with 0-35% EtOAc in hexane as eluent provided 1.89 g (59 % yield) of 3-(2-bromo-phenyl)-3-oxo-propionitrile as a yellow oil. 1H-NMR (d6-DMSO) δ: 11.8 (broad m, 1H, tautomers), 7.73 (broad s, 1H), 7.42 (m, 3H), 4.99 (s, 0.3H, tautomer), 4.64 (s, 0.6H, tautomer); HPLC/MS m/z: 223.9, 225.9 [MH]+.
Workup
- temperatureThe reaction mixture was refluxed for 1.5 hour
- customquenched with water (1 mL)
- concentrationconcentrated in vacuo
- additionThe residue was diluted with water
- extractionthe aqueous layer was extracted with hexane (2×)
- extractionThe milky aqueous layer was extracted with CHCl3 (3×)
- dry with materialthe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customPurification on silica gel with 0-35% EtOAc in hexane as eluent
Sources & evidence
- ORD record
- ord-affff15bdd044483903bbf465b170102
- Source dataset
- uspto-grants-2009_01
- Patent number
- US07473783B2
Reaction notes
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